This project involves (1) the development of a novel instrument for optical imaging of the human breast, and (2) pilot clinical tests to demonstrate the effectiveness of the proposed instrument in detecting breast cancer and monitoring response to neoadjuvant therapy of breast cancer. The proposed instrument features levels of spatial sampling (25 points/cm2 on the x-y scanning plane), spectral sampling (0.5 points/nm over the wavelength band 650-1000 nm), and temporal resolution (20 full spectra/s) that are not simultaneously achieved by any existing optical mammography instrument. These instrumentation capabilities will be used to enhance the information content of optical mammograms in terms of spatial information (depth discrimination, tomographic reconstruction of hemoglobin/water/lipid/scattering-parameters distributions), quantitative oximetry, and temporal hemodynamics characterization. The planned clinical tests will specifically test the hypothesis that intrinsic optical contrast provided by hemoglobin, water, lipids, and scattering parameters in breast tissue allows for the detection of breast cancer, its discrimination from benign breast lesions, and for monitoring effectiveness of neoadjuvant breast cancer therapy. The broad objective of this application is the development of optical mammography as a stand-alone clinical tool for breast cancer detection, and for monitoring effectiveness of therapy.